US Secretary of State Mike Pompeo on Monday threatened to place "the strongest sanctions in history" on Iran if its government does not change course.
Speaking in Washington, he called for a new nuclear agreement with Tehran following President Donald Trump's withdrawal from the 2015 deal and laid out 12 "basic requirements" for the Islamic republic.
It was Mr Pompeo's first major foreign policy address since moving to the State Department from the CIA.
Defending Mr Trump's decision to withdraw from the nuclear agreement, the recently-appointed Secretary of State said the deal was "a loser" with huge negative repercussions.
Iran had "advanced its march across the Middle East" since the deal was enacted and that the Obama administration "made a bet" that Iran would stop rogue actions and adhere to global norms, he said.
President Trump, added Mr Pompeo, withdrew from the deal because it failed to guarantee Americans' safety from the risks posed by Iran. He says the deal "put the world at risk because of its fatal flaws."
The US is willing to lift all sanctions, restore full diplomatic and commercial ties as long as Iran is willing to make "major changes," Mr Pompeo said during the speech at the conservative Heritage Foundation.
He said Iran must "stop enrichment" of uranium, which was allowed within strict limitations under the 2015 deal. Iran must also allow nuclear "unqualified access to all sites throughout the country," Mr Pompeo said, alluding to military sites that were off-limits under the 2015 deal except under specific circumstances.
To that end, he also said Iran must declare all previous efforts to build a nuclear weapon, reopening an issue that the UN's International Atomic Energy Agency has already deemed a closed matter.
Mr Pompeo also demanded Iran stop a range of activities throughout the Middle East that have long drawn the ire of the United States and its allies. He said Iran must end support for Shiite Houthi rebels in Yemen, "withdraw all forces" from Syria, halt support for its ally Hezbollah and stop threatening Israel.
Iran must also "release all US citizens" missing in Iran or being held on "spurious charges," he said.